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Article(id=1240651440075633548, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240651438955754377, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202402002, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1706716800000, receivedDateStr=2024-02-01, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773723953502, onlineDateStr=2026-03-17, pubDate=1719244800000, pubDateStr=2024-06-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773723953502, onlineIssueDateStr=2026-03-17, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773723953502, creator=13701087609, updateTime=1773723953502, updator=13701087609, issue=Issue{id=1240651438955754377, tenantId=1146029695717560320, journalId=1227665162245664772, year='2024', volume='51', issue='12', pageStart='2113', pageEnd='2912', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773723953236, creator=13701087609, updateTime=1773723953236, updator=13701087609, preIssue=null, nextIssue=null, ext=null, issueFiles=null}, startPage=2133, endPage=2139, ext={EN=ArticleExt(id=1240651440318903184, articleId=1240651440075633548, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Heterogeneous trajectory of sarcopenia and associated factors among older adults with multimorbidity: an empirical study based on CHARLS survey data, columnId=1228016567443718970, journalTitle=Modern Preventive Medicine, columnName=Epidemiology and Statistical Methods Advances, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate heterogeneous trajectory of sarcopenia and its associated factors among older adults with multimorbidity.

Methods

Based on the Asian Working Group for Sarcopenia 2019 Consensus, three waves of data in 2011, 2013, and 2015 from the China Health and Retirement Longitudinal Study were utilized. Latent growth mixture model and multinomial logistic regression were selected to identify heterogeneous sarcopenia trajectories and associated factors among older adults with multimorbidity.

Results

Of the 1 254 participants, four heterogeneous trajectories of sarcopenia were identified: high initial but sharply declining trajectory (7.5%,n=93), low and stable change trajectory (64.0%, n=803), high and stable change trajectory (23.5%, n=295), low initial but sharply increasingtrajectory (5.0%, n=63). Disability, body mass index (BMI), cognition, sleep duration, smoking habits, and alcohol consumption were associated with different sarcopenia trajectories.

Conclusion

There are heterogenous sarcopenia trajectories among older adults with multimorbidity, targeted intervention regarding disability, BMI, cognition, sleep, smoking, and drinking should conducted to prevent sarcopenia.

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目的

探究共病老人肌少症异质性轨迹，分析影响因素。

方法

数据来自中国健康与养老追踪调查（CHARLS）2011、2013和2015年3期数据。采用亚洲肌少症2019版共识诊断肌少症。利用增长混合模型探究共病老人肌少症异质性轨迹，logistic回归分析其影响因素。

结果

纳入1 254名共病老人，识别4条异质性轨迹：高风险-急速下降组（7.5%，n=93）、低风险-平稳发展组（64.0%，n=803）、高风险-平稳发展组（23.5%，n=295）、低风险-急速上升组（5.0%，n=63）。Logistic回归提示自理能力、体质指数、认知功能、睡眠时长、吸烟和饮酒是肌少症异质性轨迹影响因素。

结论

共病老人肌少症发展存在异质性轨迹，应根据不同轨迹制定对应干预策略。保持合理睡眠时长和BMI范围、预防自理和认知功能损伤、鼓励戒烟和适量饮酒利于防止共病老人肌少症呈现恶化发展轨迹。

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程丽，E-mail:
, copyrightStatement=本刊刊出的所有文章不代表中华预防医学会和本刊编委会的观点，除非特别声明。, copyrightOwner=中华预防医学会和四川大学华西公共卫生学院, extLink=null, articleAbsUrl=null, sourceXml=TK00zOx5HfvqLzXuKgv7JA==, magXml=ThcfYe/q0G4/BTkmw4Vycg==, pdfUrl=null, pdf=B3B3tlOLsq8ma25jpBnfDg==, pdfFileSize=1004288, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=soGaF05WcXKZh93oaDEmUA==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=3+Wb/0iuXsfRUrbgbDHghQ==, mapNumber=null, authorCompany=null, fund=null, authors=

刘巧（1999—），女，硕士在读，研究方向：慢病管理

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刘巧（1999—），女，硕士在读，研究方向：慢病管理

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刘巧（1999—），女，硕士在读，研究方向：慢病管理

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BMC Geriatr, 2023, 23(1): 853., articleTitle=Impact of a wearable-based physical activity and sleep intervention in multimorbidity patients: protocol for a randomized controlled trial, refAbstract=null)], funds=[Fund(id=1240651449936441763, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, awardId=2023A1515012522, language=CN, fundingSource=广东省基础与应用基础研究基金资助项目(2023A1515012522), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1240651443435271137, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, xref=null, ext=[AuthorCompanyExt(id=1240651443447854053, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, companyId=1240651443435271137, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Nursing, Sun Yat-sen University, Guangzhou, Guangdong 510000, China), AuthorCompanyExt(id=1240651443452048355, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, companyId=1240651443435271137, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=中山大学护理学院，广东 广州 510000)])], figs=[ArticleFig(id=1240651446241259740, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, language=EN, label=Fig.1, caption=The selection process of participants, figureFileSmall=pzzDrrS+ZIuTURmXMPfmsQ==, figureFileBig=soGaF05WcXKZh93oaDEmUA==, tableContent=null), ArticleFig(id=1240651446333534440, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, language=CN, label=图1, caption=研究对象筛选流程图, figureFileSmall=pzzDrrS+ZIuTURmXMPfmsQ==, figureFileBig=soGaF05WcXKZh93oaDEmUA==, tableContent=null), ArticleFig(id=1240651448002867456, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, language=EN, label=Fig.2, caption=Heterogeneous trajectory of sarcopenia among older adults with multimorbidity, figureFileSmall=I2iV7YPeNONrHunLAGwhog==, figureFileBig=kQBJ8SVRVCeaN1A7vGLD+g==, tableContent=null), ArticleFig(id=1240651448145473803, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, language=CN, label=图2, caption=共病老人肌少症异质性轨迹, figureFileSmall=I2iV7YPeNONrHunLAGwhog==, figureFileBig=kQBJ8SVRVCeaN1A7vGLD+g==, tableContent=null), ArticleFig(id=1240651448254525716, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, language=EN, label=Table 1, caption=

Baseline characteristics of older adults with multimorbidity（N=1 254）

, figureFileSmall=null, figureFileBig=null, tableContent=
变量总共(n, %)无肌少症(n, %)可能肌少症(n, %)肌少症(n, %)严重肌少症(n, %)P值
年龄(岁,)67.13±5.6465.99±5.0668.11±6.0068.39±5.7671.46±6.22<0.001
性别0.006
男性603(48.09)388(50.59)51(48.57)112(39.16)38(54.17)
女性651(51.91)379(49.41)54(51.43)174(60.84)27(45.83)
婚姻状况<0.001
已婚1 016(81.02)646(84.22)78(74.29)226(79.02)66(68.75)
离婚/未婚/丧偶254(18.98)121(15.78)27(25.71)60(20.98)30(31.25)
户口<0.001
农业1 006(80.22)574(74.84)90(85.71)261(91.26)81(84.38)
非农业250(19.78)193(25.16)15(14.29)25(8.74)15(15.63)
教育程度<0.001
文盲407(32.46)207(26.99)44(41.90)112(39.16)44(45.83)
非文盲847(67.54)560(73.01)61(58.10)174(60.84)52(54.17)
吸烟情况0.137
否890(70.97)549(71.76)82(78.85)191(67.02)68(71.58)
是359(28.63)216(28.24)22(21.15)94(32.98)27(28.42)
饮酒情况0.060
否912(72.73)549(71.58)82(78.85)202(70.88)79(82.29)
是340(27.11)218(28.42)22(21.15)83(29.12)17(17.71)
身体活动水平0.023
高水平247(19.70)147(19.17)12(11.43)68(23.78)20(20.83)
中水平215(17.15)147(19.17)20(19.05)38(13.29)10(10.42)
低水平792(63.16)473(61.66)73(69.52)180(62.94)66(68.75)
自理能力受损<0.001
否987(78.71)636(82.92)67(63.81)225(78.67)59(61.46)
是267(21.29)131(17.08)38(36.19)61(21.33)37(38.54)
抑郁情绪<0.001
否601(47.93)408(53.26)43(40.95)118(41.26)32(33.33)
是651(51.99)358(46.74)62(59.05)168(58.74)64(66.67)
共病数量(个)0.002
2~3986(78.63)597(77.84)70(66.67)240(83.92)79(82.29)
≥4268(21.37)170(22.16)35(33.33)46(16.08)17(17.71)
睡眠时长(小时,)6.02±2.046.12±1.966.25±1.825.80±2.185.59±2.330.015
BMI(kg/m2,)23.40±4.0325.14±3.4525.34±3.1519.35±1.7919.35±1.81<0.001
健康状况自我报告(分,)3.30±0.793.24±0.793.48±0.753.33±0.803.46±0.720.003
认知(分,)13.05±5.6513.88±5.4311.33±5.4712.02±5.8013.35±5.98<0.001
), ArticleFig(id=1240651448359383326, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, language=CN, label=表1, caption=

共病老人的一般资料（N=1 254）

, figureFileSmall=null, figureFileBig=null, tableContent=
变量总共(n, %)无肌少症(n, %)可能肌少症(n, %)肌少症(n, %)严重肌少症(n, %)P值
年龄(岁,)67.13±5.6465.99±5.0668.11±6.0068.39±5.7671.46±6.22<0.001
性别0.006
男性603(48.09)388(50.59)51(48.57)112(39.16)38(54.17)
女性651(51.91)379(49.41)54(51.43)174(60.84)27(45.83)
婚姻状况<0.001
已婚1 016(81.02)646(84.22)78(74.29)226(79.02)66(68.75)
离婚/未婚/丧偶254(18.98)121(15.78)27(25.71)60(20.98)30(31.25)
户口<0.001
农业1 006(80.22)574(74.84)90(85.71)261(91.26)81(84.38)
非农业250(19.78)193(25.16)15(14.29)25(8.74)15(15.63)
教育程度<0.001
文盲407(32.46)207(26.99)44(41.90)112(39.16)44(45.83)
非文盲847(67.54)560(73.01)61(58.10)174(60.84)52(54.17)
吸烟情况0.137
否890(70.97)549(71.76)82(78.85)191(67.02)68(71.58)
是359(28.63)216(28.24)22(21.15)94(32.98)27(28.42)
饮酒情况0.060
否912(72.73)549(71.58)82(78.85)202(70.88)79(82.29)
是340(27.11)218(28.42)22(21.15)83(29.12)17(17.71)
身体活动水平0.023
高水平247(19.70)147(19.17)12(11.43)68(23.78)20(20.83)
中水平215(17.15)147(19.17)20(19.05)38(13.29)10(10.42)
低水平792(63.16)473(61.66)73(69.52)180(62.94)66(68.75)
自理能力受损<0.001
否987(78.71)636(82.92)67(63.81)225(78.67)59(61.46)
是267(21.29)131(17.08)38(36.19)61(21.33)37(38.54)
抑郁情绪<0.001
否601(47.93)408(53.26)43(40.95)118(41.26)32(33.33)
是651(51.99)358(46.74)62(59.05)168(58.74)64(66.67)
共病数量(个)0.002
2~3986(78.63)597(77.84)70(66.67)240(83.92)79(82.29)
≥4268(21.37)170(22.16)35(33.33)46(16.08)17(17.71)
睡眠时长(小时,)6.02±2.046.12±1.966.25±1.825.80±2.185.59±2.330.015
BMI(kg/m2,)23.40±4.0325.14±3.4525.34±3.1519.35±1.7919.35±1.81<0.001
健康状况自我报告(分,)3.30±0.793.24±0.793.48±0.753.33±0.803.46±0.720.003
认知(分,)13.05±5.6513.88±5.4311.33±5.4712.02±5.8013.35±5.98<0.001
), ArticleFig(id=1240651448451658024, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, language=EN, label=Table 2, caption=

Total number of observed transitions over a 4-year follow-up

, figureFileSmall=null, figureFileBig=null, tableContent=
状态从
无肌少症可能肌少症肌少症严重肌少症
无肌少症1246 (82.03%)122 (46.74%)86 (15.50%)14 (7.57%)
可能肌少症182 (11.98%)95 (36.40%)23 (4.14%)21 (11.35%)
肌少症74 (4.87%)23 (8.81%)345 (62.16%)64(34.59%)
严重肌少症17 (1.12%)21 (8.05%)101 (18.20%)86 (46.49%)
), ArticleFig(id=1240651448581681460, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, language=CN, label=表2, caption=

肌少症各状态4年转换次数

, figureFileSmall=null, figureFileBig=null, tableContent=
状态从
无肌少症可能肌少症肌少症严重肌少症
无肌少症1246 (82.03%)122 (46.74%)86 (15.50%)14 (7.57%)
可能肌少症182 (11.98%)95 (36.40%)23 (4.14%)21 (11.35%)
肌少症74 (4.87%)23 (8.81%)345 (62.16%)64(34.59%)
严重肌少症17 (1.12%)21 (8.05%)101 (18.20%)86 (46.49%)
), ArticleFig(id=1240651448678150460, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, language=EN, label=Table 3, caption=

Fitted indices for GMMs with 1 to 6 classes of sarcopenia trajectories among older adults with multimorbidity

, figureFileSmall=null, figureFileBig=null, tableContent=
模型Pearson χ2AICBICaBICEntropyLMR
(P)		BLRT
(P)		人数类别概率
1-4531.5689079.1379120.2109094.798///12541
2-3955.4387932.8767989.3517954.4100.987<0.0001<0.0001384/8700.306/0.694
3-3827.7367683.4737755.3507710.8800.9770.0004<0.0001859/313/820.685/0.250/0.065
4-3576.4637186.9267274.2067220.2060.987<0.0001<0.000193/803/295/630.075/0.640/0.235/0.050
5-3465.4106970.8207073.5027009.9720.9880.0092<0.0001715/69/88/291/910.570/0.055/0.070/0.232/0.073
6-3448.9776943.9537062.0386988.9790.9860.02240.2398803/52/84/17/81/170.640/0.041/0.067/0.014/0.065/0.173
), ArticleFig(id=1240651448820756812, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, language=CN, label=表3, caption=

老年共病患者肌少症异质性轨迹的GMM拟合信息

, figureFileSmall=null, figureFileBig=null, tableContent=
模型Pearson χ2AICBICaBICEntropyLMR
(P)		BLRT
(P)		人数类别概率
1-4531.5689079.1379120.2109094.798///12541
2-3955.4387932.8767989.3517954.4100.987<0.0001<0.0001384/8700.306/0.694
3-3827.7367683.4737755.3507710.8800.9770.0004<0.0001859/313/820.685/0.250/0.065
4-3576.4637186.9267274.2067220.2060.987<0.0001<0.000193/803/295/630.075/0.640/0.235/0.050
5-3465.4106970.8207073.5027009.9720.9880.0092<0.0001715/69/88/291/910.570/0.055/0.070/0.232/0.073
6-3448.9776943.9537062.0386988.9790.9860.02240.2398803/52/84/17/81/170.640/0.041/0.067/0.014/0.065/0.173
), ArticleFig(id=1240651448908837204, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, language=EN, label=Table 4, caption=

Estimates and tests of intercept and slope for latent classes among older adults with multimorbidity

, figureFileSmall=null, figureFileBig=null, tableContent=
组别例数截距 (intercept)斜率 (slope)
估计值标准误t值P值估计值标准误t值P值
高风险-急速下降组932.1980.04944.782<0.001-0.4840.013-36.928<0.001
低风险-平稳发展组8030.1170.01110.791<0.0010.0190.0044.950<0.001
高风险-平稳发展组2952.2100.02783.326<0.0010.0280.0093.2790.001
低风险-急速上升组630.1620.0543.0140.0030.5220.01731.258<0.001
), ArticleFig(id=1240651449009500511, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, language=CN, label=表4, caption=

老年共病患者肌少症各潜在类别的截距和斜率估计值及其检验结果

, figureFileSmall=null, figureFileBig=null, tableContent=
组别例数截距 (intercept)斜率 (slope)
估计值标准误t值P值估计值标准误t值P值
高风险-急速下降组932.1980.04944.782<0.001-0.4840.013-36.928<0.001
低风险-平稳发展组8030.1170.01110.791<0.0010.0190.0044.950<0.001
高风险-平稳发展组2952.2100.02783.326<0.0010.0280.0093.2790.001
低风险-急速上升组630.1620.0543.0140.0030.5220.01731.258<0.001
), ArticleFig(id=1240651449110163823, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, language=EN, label=Table 5, caption=

Assignment of categorical variables

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自变量赋值情况
吸烟1=吸烟 0=不吸烟
饮酒1=饮酒 0=不饮酒
身体活动高水平（Z1=1，Z2=0），中水平（Z1=0，Z2=0），低水平（Z1=0，Z2=1）
自理能力受损1=有 0=无
抑郁情绪1=有 0=无
), ArticleFig(id=1240651449282130294, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, language=CN, label=表5, caption=

分类自变量赋值情况

, figureFileSmall=null, figureFileBig=null, tableContent=
自变量赋值情况
吸烟1=吸烟 0=不吸烟
饮酒1=饮酒 0=不饮酒
身体活动高水平（Z1=1，Z2=0），中水平（Z1=0，Z2=0），低水平（Z1=0，Z2=1）
自理能力受损1=有 0=无
抑郁情绪1=有 0=无
), ArticleFig(id=1240651449391182205, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, language=EN, label=Table 6, caption=

Associated factors with heterogeneous sarcopenia trajectories among older adults with multimorbidity using Multinomial Logit Regression

, figureFileSmall=null, figureFileBig=null, tableContent=
变量高风险-急速下降组高风险-平稳发展组低风险-急速上升组
OR(95%CI)POR(95%CI)POR(95%CI)P
吸烟情况
否------
是0.22(0.11~0.45)<0.0010.26(0.14~0.48)<0.0011.03(0.56~1.90)0.936
饮酒情况
否------
是0.33(0.16~0.67)0.0020.39(0.21~0.71)0.0020.40(0.19~0.83)0.014
身体活动水平
高水平1.03(0.38~2.79)0.9530.84(0.35~1.99)0.6841.43(0.85~2.40)0.493
中水平------
低水平1.06(0.44~2.53)0.9020.89(0.42~1.88)0.7522.00(1.31~3.05)0.102
自理能力受损
否------
是2.48(1.13~5.44)0.0234.80(2.45~9.40)<0.0011.17(0.61~2.24)0.638
抑郁情绪
否------
是1.11(0.58~2.10)0.7600.98(0.56~1.72)0.9511.16(0.65~2.05)0.615
共病数量(个)
2~3------
≥40.79(0.35~1.80)0.5720.86(0.42~1.76)0.6810.98(0.52~1.86)0.951
睡眠时长(小时)0.81(0.70~0.94)0.0060.89(0.78~1.01)0.0760.98(0.86~1.12)0.788
BMI(kg/m2)0.19(0.15~0.25)<0.0010.14(0.11~0.18)<0.0010.76(0.68~0.86)<0.001
自我报告健康状况0.79(0.52~1.20)0.2650.77(0.54~1.11)0.1651.08(0.75~1.55)0.698
认知0.97(0.92~1.02)0.2560.92(0.87~0.97)0.0010.95(0.90~0.99)0.030
), ArticleFig(id=1240651449483456902, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, language=CN, label=表6, caption=

肌少症异质性轨迹的无序多分类logistic分析结果

, figureFileSmall=null, figureFileBig=null, tableContent=
变量高风险-急速下降组高风险-平稳发展组低风险-急速上升组
OR(95%CI)POR(95%CI)POR(95%CI)P
吸烟情况
否------
是0.22(0.11~0.45)<0.0010.26(0.14~0.48)<0.0011.03(0.56~1.90)0.936
饮酒情况
否------
是0.33(0.16~0.67)0.0020.39(0.21~0.71)0.0020.40(0.19~0.83)0.014
身体活动水平
高水平1.03(0.38~2.79)0.9530.84(0.35~1.99)0.6841.43(0.85~2.40)0.493
中水平------
低水平1.06(0.44~2.53)0.9020.89(0.42~1.88)0.7522.00(1.31~3.05)0.102
自理能力受损
否------
是2.48(1.13~5.44)0.0234.80(2.45~9.40)<0.0011.17(0.61~2.24)0.638
抑郁情绪
否------
是1.11(0.58~2.10)0.7600.98(0.56~1.72)0.9511.16(0.65~2.05)0.615
共病数量(个)
2~3------
≥40.79(0.35~1.80)0.5720.86(0.42~1.76)0.6810.98(0.52~1.86)0.951
睡眠时长(小时)0.81(0.70~0.94)0.0060.89(0.78~1.01)0.0760.98(0.86~1.12)0.788
BMI(kg/m2)0.19(0.15~0.25)<0.0010.14(0.11~0.18)<0.0010.76(0.68~0.86)<0.001
自我报告健康状况0.79(0.52~1.20)0.2650.77(0.54~1.11)0.1651.08(0.75~1.55)0.698
认知0.97(0.92~1.02)0.2560.92(0.87~0.97)0.0010.95(0.90~0.99)0.030
), ArticleFig(id=1240651449642840467, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, language=EN, label=Table 7, caption=

Associated factors with heterogeneous sarcopenia trajectories among older adults with multimorbidity using Multinomial Logit Regression (complete case analysis)

, figureFileSmall=null, figureFileBig=null, tableContent=
变量高风险-急速下降组高风险-平稳发展组低风险-急速上升组
OR (95%CI)POR (95%CI)POR (95%CI)P
吸烟情况
否------
是0.23 (0.11~0.46)<0.0010.27 (0.15~0.50)<0.0011.05 (0.57~1.95)0.869
饮酒情况
否------
是0.33 (0.16~0.68)0.0030.39 (0.21~0.73)0.0030.40 (0.19~0.83)0.015
身体活动水平
高水平1.13 (0.41~3.11)0.8110.83 (0.35~1.96)0.6661.41 (0.51~3.90)0.512
中水平------
低水平1.16 (0.48~2.83)0.7450.87 (0.41~1.85)0.7212.05 (0.90~4.71)0.090
自理能力受损
否------
是2.53 (1.15~5.56)0.0214.64 (2.36~9.13)<0.0011.16 (0.60~2.26)0.656
抑郁情绪
否------
是1.04 (0.54~1.98)0.9121.01 (0.57~1.78)0.9701.11 (0.63~1.97)0.716
共病数量 (个)
2~3------
≥40.84 (0.37~1.92)0.6740.88 (0.43~1.83)0.7361.01 (0.52~1.96)0.984
睡眠时长 (小时)0.82 (0.71~0.95)0.0080.89 (0.78~1.01)0.0800.99 (0.87~1.12)0.842
BMI (Kg/m2)0.19 (0.15~0.25)<0.0010.15 (0.11~0.19)<0.0010.76 (0.68~0.86)<0.001
自我报告健康状况0.78 (0.52~1.19)0.2460.78 (0.54~1.12)0.1731.07 (0.74~1.55)0.712
认知0.96 (0.91~1.02)0.1710.92 (0.88~0.97)0.0020.94 (0.89~0.99)0.013
), ArticleFig(id=1240651449768669593, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651440075633548, language=CN, label=表7, caption=

肌少症异质性轨迹的无序多分类Logistic分析结果（完整个案分析）

, figureFileSmall=null, figureFileBig=null, tableContent=
变量高风险-急速下降组高风险-平稳发展组低风险-急速上升组
OR (95%CI)POR (95%CI)POR (95%CI)P
吸烟情况
否------
是0.23 (0.11~0.46)<0.0010.27 (0.15~0.50)<0.0011.05 (0.57~1.95)0.869
饮酒情况
否------
是0.33 (0.16~0.68)0.0030.39 (0.21~0.73)0.0030.40 (0.19~0.83)0.015
身体活动水平
高水平1.13 (0.41~3.11)0.8110.83 (0.35~1.96)0.6661.41 (0.51~3.90)0.512
中水平------
低水平1.16 (0.48~2.83)0.7450.87 (0.41~1.85)0.7212.05 (0.90~4.71)0.090
自理能力受损
否------
是2.53 (1.15~5.56)0.0214.64 (2.36~9.13)<0.0011.16 (0.60~2.26)0.656
抑郁情绪
否------
是1.04 (0.54~1.98)0.9121.01 (0.57~1.78)0.9701.11 (0.63~1.97)0.716
共病数量 (个)
2~3------
≥40.84 (0.37~1.92)0.6740.88 (0.43~1.83)0.7361.01 (0.52~1.96)0.984
睡眠时长 (小时)0.82 (0.71~0.95)0.0080.89 (0.78~1.01)0.0800.99 (0.87~1.12)0.842
BMI (Kg/m2)0.19 (0.15~0.25)<0.0010.15 (0.11~0.19)<0.0010.76 (0.68~0.86)<0.001
自我报告健康状况0.78 (0.52~1.19)0.2460.78 (0.54~1.12)0.1731.07 (0.74~1.55)0.712
认知0.96 (0.91~1.02)0.1710.92 (0.88~0.97)0.0020.94 (0.89~0.99)0.013
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共病老人肌少症异质性轨迹和影响因素研究—基于CHARLS数据的实证分析
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刘巧 , 杨巧玲 , 段娅娟 , 韩璐 , 谢琴琴 , 程丽
现代预防医学 | 流行病与统计方法 2024,51(12): 2133-2139
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现代预防医学 | 流行病与统计方法 2024, 51(12): 2133-2139
共病老人肌少症异质性轨迹和影响因素研究—基于CHARLS数据的实证分析
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刘巧, 杨巧玲, 段娅娟, 韩璐, 谢琴琴, 程丽
作者信息
  • 中山大学护理学院，广东 广州 510000

    • 刘巧（1999—），女，硕士在读，研究方向：慢病管理

通讯作者:

程丽，E-mail:
Heterogeneous trajectory of sarcopenia and associated factors among older adults with multimorbidity: an empirical study based on CHARLS survey data
Qiao LIU, Qiao-ling YANG, Ya-juan DUAN, Lu HAN, Qin-qin XIE, Li CHENG
Affiliations
  • School of Nursing, Sun Yat-sen University, Guangzhou, Guangdong 510000, China
出版时间: 2024-06-25 doi: 10.20043/j.cnki.MPM.202402002
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摘要
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目的

探究共病老人肌少症异质性轨迹，分析影响因素。

方法

数据来自中国健康与养老追踪调查（CHARLS）2011、2013和2015年3期数据。采用亚洲肌少症2019版共识诊断肌少症。利用增长混合模型探究共病老人肌少症异质性轨迹，logistic回归分析其影响因素。

结果

纳入1 254名共病老人，识别4条异质性轨迹：高风险-急速下降组（7.5%，n=93）、低风险-平稳发展组（64.0%，n=803）、高风险-平稳发展组（23.5%，n=295）、低风险-急速上升组（5.0%，n=63）。Logistic回归提示自理能力、体质指数、认知功能、睡眠时长、吸烟和饮酒是肌少症异质性轨迹影响因素。

结论

共病老人肌少症发展存在异质性轨迹，应根据不同轨迹制定对应干预策略。保持合理睡眠时长和BMI范围、预防自理和认知功能损伤、鼓励戒烟和适量饮酒利于防止共病老人肌少症呈现恶化发展轨迹。

共病老人  /  肌少症  /  异质性轨迹  /  影响因素
Objective

To investigate heterogeneous trajectory of sarcopenia and its associated factors among older adults with multimorbidity.

Methods

Based on the Asian Working Group for Sarcopenia 2019 Consensus, three waves of data in 2011, 2013, and 2015 from the China Health and Retirement Longitudinal Study were utilized. Latent growth mixture model and multinomial logistic regression were selected to identify heterogeneous sarcopenia trajectories and associated factors among older adults with multimorbidity.

Results

Of the 1 254 participants, four heterogeneous trajectories of sarcopenia were identified: high initial but sharply declining trajectory (7.5%,n=93), low and stable change trajectory (64.0%, n=803), high and stable change trajectory (23.5%, n=295), low initial but sharply increasingtrajectory (5.0%, n=63). Disability, body mass index (BMI), cognition, sleep duration, smoking habits, and alcohol consumption were associated with different sarcopenia trajectories.

Conclusion

There are heterogenous sarcopenia trajectories among older adults with multimorbidity, targeted intervention regarding disability, BMI, cognition, sleep, smoking, and drinking should conducted to prevent sarcopenia.

Older adults with multimorbidity  /  Sarcopenia  /  Heterogeneous trajectory  /  Associatedfactors
刘巧, 杨巧玲, 段娅娟, 韩璐, 谢琴琴, 程丽. 共病老人肌少症异质性轨迹和影响因素研究—基于CHARLS数据的实证分析. 现代预防医学, 2024 , 51 (12) : 2133 -2139 . DOI: 10.20043/j.cnki.MPM.202402002
Qiao LIU, Qiao-ling YANG, Ya-juan DUAN, Lu HAN, Qin-qin XIE, Li CHENG. Heterogeneous trajectory of sarcopenia and associated factors among older adults with multimorbidity: an empirical study based on CHARLS survey data[J]. Modern Preventive Medicine, 2024 , 51 (12) : 2133 -2139 . DOI: 10.20043/j.cnki.MPM.202402002
正文
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肌少症指与增龄有关的肌肉质量减少合并肌肉力量和（或）躯体功能下降的老年综合征[1]。肌少症导致跌倒、功能受限等不良结局，导致照护支出急剧上升[1]。亚洲肌少症2019版共识（the Asian Working Group for Sarcopenia 2019 consensus, AWGS 2019）提示肌少症分四种状态：无肌少症、可能肌少症、肌少症和严重肌少症[1-2]。共病（Multimorbidity）指同一个体身上同时存在2种和（或）以上慢性健康问题，需给予复杂和持续的干预[3-4]。共病增加老人临床诊疗复杂性和多重用药等不良结局风险[4]。共病和多重用药被视作肌少症独立预测因素[5-6]。Dodds等的研究提示共病者发生可能肌少症的风险是非共病者的1.96倍[7]。崔玉珠等的研究表明我国中老年人可能肌少症发生率为21.56%，共病者发生可能肌少症风险远高于非共病者[8]。肌少症发展呈动态性和可逆性，不同状态转换受健康行为等多因素影响[8-11]。Trevisan等和Murphy等的研究提示不同个体肌少症状态间存在双向转换[9, 12]。而目前共病老人肌少症发展趋势仍不清楚，识别共病老人肌少症异质性轨迹利于早期发现易感个体，探究其异质轨迹影响因素利于个体在特定时期的精确干预。故本研究旨在探究共病老人肌少症异质性轨迹，分析其影响因素，为预防共病人群发生肌少症提供参考。
1　对象与方法
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1.1　研究对象
本研究数据为中国健康与养老追踪调查（the China Health and Retirement Longitudinal Study, CHARLS）2011、2013和2015年三期数据[13]。纳入标准：（1）基线年龄≥60岁；（2）诊断共病（≥2种慢病）；（3）完整三年肌少症数据。排除标准：（1）患精神疾病或认知障碍；（2）诊断恶性肿瘤。本研究最终纳入1 254名研究对象，获得北京大学伦理审批（IRB00001052-11015）。具体的研究对象纳入和排除流程见图1。
1.2　研究内容
基于AWGS 2019，通过肌肉力量、肌肉质量和躯体功能定义肌少症[1-2]。（1）肌肉力量：使用握力体现。肌肉力量下降为男性握力<28 kg、女性握力<18 kg。（2）肌肉质量：CHARLS未测量受访者肌肉质量，本研究基于Wen等的研究估计四肢肌肉质量（the Appendicular Skeletal Muscle Mass, ASM）[14]。ASM=0.193×体重（kg）+ 0.107×身高（cm）-4.157×性别-0.037×年龄-2.631。同时采用身高校正四肢肌肉质量（ASM/height2）评估肌肉质量，男性<7.0 kg/m2、女性<5.4 kg/m2为肌肉质量下降。（3）躯体功能：使用2.5米步行实验和5次座椅实验评估。步速<1 m/s或5次座椅实验时间>12 s或无法完成测试者为躯体功能下降。可能肌少症为仅出现肌肉力量和（或）躯体功能降低。肌少症为肌肉质量下降合并躯体功能或肌肉质量下降合并肌肉力量下降。严重肌少症为肌肉质量、躯体功能、肌肉力量下降。无上述三种状况者为无肌少症。按照肌少症严重程度，将无肌少症至严重肌少症依次编码为0~3。解释变量包括一般资料、生活方式、身体活动、自理能力、抑郁情绪、认知功能。
①身体活动：由于CHARLS中身体活动部分问卷和《国际身体活动问卷》较相似，我们基于《国际身体活动问卷-简版》（the short version of International Physical Activity Questionnaire, IPAQ-SF）构造了身体活动水平的变量[15]。身体活动水平包括活动强度（剧烈、中等和步行），持续时间（≥4h，2-4h，0.5-2h，＜0.5h），以及运动时长（1-7天）。身体活动持续时间根据区间的最小值进行编码，依次为4h、3h、1.25h和0.5h。基于IPAQ-SF使用代谢当量对不同强度水平的量进行定义：剧烈、中等和步行活动的代谢当量分别为8、4和3.3单位。因此，个人的身体活动水平=8.0×剧烈活动持续时间×天数+ 4.0×剧烈活动持续时间×天数+ 3.3×剧烈活动持续时间×天数。最终身体活动水平分为三个亚组：高水平、中等水平和低水平。
②自理能力评估：通过基本日常生活活动和工具性日常生活活动评估自理能力。日常生活活动包括6项内容：穿衣、洗澡、吃饭、上下床、如厕、控制小便和排便[16]。工具性日常生活活动包括5项内容：理财、服药、购物、做饭和做家务[17]。回答依次包括4个选项：没有困难、有困难但仍然可以做到、有困难并需要帮助、不能做到。凡在任意一项内容中报告“有困难并需要帮助”或“不能做到”者视为自理能力受损。
③抑郁情绪评估：通过美国流行病学研究中心抑郁量表 （The Center for Epidemiologic Studies Depression Scale, CES-D）评估老年人抑郁情绪[18]。CES-D量表包括10个条目，测量受访者在过去一周的经历。每个项目的评分为4分，范围从“很少或没有时间”（0分）到“一直”（3分），其中条目5和8需要反向计分，总分在0 ~ 30分之间，得分越高表明抑郁情绪越严重。在本研究中，≥10分认为属于抑郁情绪。
④认知功能评估：通过两个维度来评估认知功能[19]。第一个维度是情景记忆，包括即时单词回忆（0-10分）和延迟单词回忆（0-10分）。另一个维度是心理状态，心理状态分为定向、视觉建构和注意三个部分。受访者被要求说出今天的日期（月、日、年和季节）和星期几以评估定向（0-5分）；通过测试重新绘制先前显示的图形的能力来衡视觉构建（0-1分）；参与者通过连续5次从100减去7来评估注意力（0-5分）。认知功能总分0 ~ 31分，得分越高，认知功能越好。
1.3　统计学分析
使用Stata 17.0、SPSS 26.0、Mplus 8.3进行数据整理和分析。采用多状态马尔可夫模型（Multistate Markov Model）探究个体肌少症不同状态的转化情况。采用增长混合模型（Growth Mixture Model, GMM）探究异质性轨迹。GMM可识别群体中潜在类别，在每个类别组内构建不同增长轨迹描述个体随时间变化情况。该模型评价指标：（1）艾凯克信息准则（AIC）、贝叶斯信息准则（BIC）、样本校正的 BIC（aBIC）；（2）熵（Entropy）；（3）检验统计量：似然比检验指标 （LMR） 和基于Bootstrap 的似然比检验（BLRT）指标。遵从“信息学指标越小、Entropy越大、LMR和BLRT达显著水平”原则，基于理论、临床意义和可解释性等综合选择最佳模型。GMM中截距和斜率均存在均数和方差两个参数。确定最佳类别模型后，以肌少症异质性轨迹为因变量，在控制一般资料情况下，纳入生活方式等协变量进行logistic回归分析探究轨迹影响因素。检验水准为0.05。缺失值采用多重插补处理，敏感性分析检验结果可靠性。
2　结果
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2.1　基本特征
1 254名共病老人中男性和女性分别为603和651例。基线无肌少症、可能肌少症、肌少症、严重肌少症者分别为767、105、286、96例。无肌少症、可能肌少症、肌少症和严重肌少症的中共病个数≥4种的例数分别为170、35、46、17例。详见表1。
2.2　共病老人肌少症转换次数
共病老人肌少症4年间共发生2 508次转换。无肌少症者在4年间进展为可能肌少症概率为11.98%。可能肌少症者进展为肌少症和逆转为无肌少症的4年概率分别8.81%和46.74%。详见表2。
2.3　共病老人肌少症异质性轨迹
拟合1~6个类别GMM，结果显示随类别数量增加，信息学指标逐渐递减，4类别Entropy最大，且BIC值在类别4处存在拐点。结合模型可解释性等选择4类别模型，详见表3。
4条共病老人肌少症异质性轨迹详见图2。各轨迹分别命名：高风险-急速下降组（n=93）、低风险-平稳发展组（n=803）、高风险-平稳发展组（n=295）、低风险-急速上升组（n=63）。详见表4。
2.4　共病老人肌少症异质性轨迹影响因素
以共病老人肌少症异质性轨迹为因变量，其中低风险-平稳发展组为参考组，在控制一般资料情况下，纳入生活方式等协变量作无序多分类logistic回归分析。连续变量以原值输入，分类自变量详见表5。
结果提示与低风险-平稳发展组相比，吸烟（OR=0.22, 95%CI=0.11~0.45, P<0.001）、饮酒（OR=0.33, 95%CI=0.16~0.67, P=0.002）、睡眠时间越长（OR=0.81, 95%CI=0.70~0.94, P=0.006）、BMI越高者（OR=0.19, 95%CI=0.15~0.25, P<0.001）越不容易进入高风险-急速下降组，而存在自理能力受损者（OR=2.48, 95%CI=1.13~5.44, P=0.023）更容易进入高风险-急速下降组；吸烟（OR=0.26, 95%CI=0.14~0.48, P<0.001）、饮酒（OR=0.39, 95%CI=0.21~0.71, P=0.002）、BMI越高（OR=0.14, 95%CI=0.11~0.18, P<0.001）、认知功能越好者（OR=0.92, 95%CI=0.87~0.97, P=0.001）越不容易进入高风险-平稳发展组，而存在自理能力受损者（OR=4.80, 95%CI=2.45~9.40, P<0.001）更容易进入高风险-平稳发展组；饮酒（OR=0.40, 95%CI=0.19~0.83, P=0.014）、BMI越高（OR=0.76, 95%CI=0.68~0.86, P<0.001）、认知功能越好者（OR=0.95, 95%CI=0.90~0.99, P=0.030）越不容易进入高风险-平稳发展组。详见表6。
敏感性分析提示多重插补和完整个案分析参数估计相似，详见表7。
3　讨论
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本研究发现共病老人肌少症发展呈动态、可逆性。我国可能肌少症逆转无肌少症次数（46.74%）远高于达进展为肌少症次数（8.81%）。尽管有诊断标准差异，Sun等的研究也提示我国健康老年人可能肌少症逆转为无肌少症占比最高（41.50%）[20]。故可能肌少症是最佳干预窗口期，需开展早期筛查以发现高风险人群。Trevisan等的研究也提示可能肌少症在12年追踪期间逆转为无肌少症次数（9.16%）和进展为肌少症次数（10.50%）类似[9]，提示可能肌少症是最动态发展的阶段，需及时干预高风险者以避免不良结局。
通过识别4条共病老人肌少症异质性轨迹，证实肌少症发展具有动态性和异质性。低风险-急速上升组提示共病老人肌少症在4年间发展飞速，既往研究提示肌少症导致众多不良结局，故该类型老人最应给予及时干预。该轨迹提示特定时间或累积危险因素可能导致肌少症快速进展，探究该轨迹的可干预因素很必要。高风险-快速下降组提示肌少症发展逆转趋势，既往研究提示肌少症发展包括进展性恶化和逆转性发展，此类轨迹提示应探究可逆性轨迹的可干预因素，从而有效指导干预[1]。高风险-平稳发展组表明肌少症初始风险较高，且呈现恶化并维持的趋势，该轨迹提示有效干预对减轻高危人群肌少症负担能产生最优效果。
本研究提示自理能力受损增加肌少症恶化风险。Gao等和Dodds等的研究都提示自理能力受损导致肌少症发病风险增加近1.5倍[10, 21]。用药是日常自理能力重要指标，对经常多重用药的共病老人，正确用药能力下降增加共病恶化程度；且共病加重日常自理能力受损，导致肌肉力量和肌肉质量降低，增加肌少症风险[6, 22]。自理能力受损提示不同程度的功能损伤和依赖、运动能力和握力下降，导致老年人参与身体活动能力降低；且自理能力受损导致共病老人社会参与能力受损，其通过身体活动、口腔健康等多条路径增加肌少症风险[23]-[25]。肌少症伴随握力低和（或）步态减慢，加深功能障碍程度，导致更多不良后果，形成恶性循环[26]。故应鼓励自理能力受损者进行被动身体活动以增强肌肉功能、防止肌肉萎缩。
本研究发现BMI越高，肌少症恶化风险越低。Trevisan等的研究提示BMI每增加一个单位，肌少症的发病风险降低25%[9]。Yu等的研究提示BMI升高会降低肌少症发病风险（OR=0.66），增加肌少症逆转可能性（OR=1.16）[24]。Morikawa等的研究提示肌少症肥胖导致自理能力下降风险增加2.48倍[27]。肥胖对肌少症的保护作用与肥胖导致新陈代谢和健康状况恶化的观点相矛盾，称“肥胖悖论”[28]。但过高体脂加剧脂肪向肌肉浸润，肌肉力量、质量和功能下降，发生肌少性肥胖导致不良结局[28]。同时肥胖通过损伤自理能力进一步加重患者的共病程度，成为共病与肌少症的协同危险因素，增加共病老人不良结局风险。故提示未来研究应探索最佳BMI范围和其他准确指示老年人超重和（或）肥胖的措施，以精准地预防共病老人肌少症发展。
本研究发现维持认知功能有助于防止肌少症呈现恶化发展趋势。Kitamura 等的研究发现认知损伤是肌少症的危险因素（OR=2.60）[26]。Hu等的研究提示肌少症患者轻度认知障碍风险比未患肌少症的患者高1.72倍[29]。认知障碍与肌少症存在共有生理基础，通过促炎细胞因子、氧化应激导致肌少症轨迹呈现恶化趋势[30]；共病增加慢性炎症风险，通过炎症浸润导致肌少症进一步恶化[24]。认知障碍改变老年人大脑结构，降低其开展身体活动能力[31]。体力活动不足是预测加速肌肉损失和肌少症恶化的重要因素[32]。且共病增加久坐行为而导致肌少症[6]。未来应探究认知功能和肌少症轨迹发展的具体机制，指导肌少症干预方案。
本研究提示睡眠时间增加利于维持肌少症低风险状态。Lee等的研究提示长睡眠时间（>8 h/晚）导致男性肌少症风险增加2.41倍[33]。Han等人发现长睡眠时长（>8h）和短睡眠时长（<6 h）者分别比正常时长者的肌少症风险高1.84、2.74倍，提示睡眠时长与肌少症风险呈“U”型关系[34]。Helbig等人的研究提示短睡眠（<5 h）导致老年女性共病风险增加2倍以上[35]。睡眠不足不仅加速肌肉蛋白水解，降低肌纤维横截面积，且阻碍生长激素分泌，导致身体成分、肌肉力量和体能下降[36]。而睡眠过长增加胰岛素抵抗，肌肉蛋白合成减少；长睡眠时间增加慢性炎症风险，与共病和肌少症存在协同机制[34,37-38]。国际睡眠组织推荐老人最佳睡眠时长为7~8小时[39]，但关于睡眠时长和肌少症轨迹的研究较少，仍需挖掘预防共病老人肌少症的最佳睡眠时长。
本研究结果提示饮酒和吸烟利于维持肌少症低风险发展轨迹。值得注意的是，该结果需要审慎地推广，既往研究多提示饮酒和吸烟通过氧化应激、慢性炎症等多种机制增加肌少症与共病的发病风险[40]。Bu等人通过开展的系统评价与Meta分析提示：饮酒对于社区老年人肌少症的患病风险具有保护作用（OR=0.84）。同时该研究提示酒量与肌少症风险存在“J”型剂量关系，肌少症风险在饮酒量每天6.6毫克时达到最低[41]。Trevisan等人的纵向研究提示：尽管统计学不存在差异，吸烟是可能肌少症恶化发展的保护因素（OR=0.77）[9]。代偿健康信念（Compensatory Health Beliefs）是指不健康行为的负面影响可以通过参与另一种健康行为来补偿或“中和”的理念，抽烟和饮酒者会通过参与其他健康行为比如保持良好的饮食习惯和营养状态、增加身体活动等来补偿由吸烟所带来的危害[42-43]。而营养状态和身体活动属于影响肌少症和共病发展的重要因素[44-45]。本研究尚未发现不同身体活动水平与肌少症异质性轨迹间的关系，可能是由于CHARLS关注受试者不同身体活动的频次和持续时间，未能准确捕捉受试者的抗阻运动频率和时间，而抗阻运动由于能缩短肌肉蛋白合成的合成时间、增强肌肉质量和力量而成为预防肌少症恶化的首选[31]。故临床医护人员应该鼓励共病老年人维持健康的生活方式，主动戒烟和适量饮酒，保持良好的饮食和运动习惯。
本研究基于CHARLS数据库分析共病老人肌少症不同状态的纵向转换，提示共病老人为肌少症高危人群，可能肌少症是重要干预窗口。共病老人肌少症异质性轨迹提示重视对该人群的早期筛查，尽早识别高危人群以避免不良结局；且不同轨迹对于干预方案制定具有指导意义。保持合适睡眠时长和BMI范围，预防自理能力受损和认知功能下降，鼓励戒烟和适当饮酒有助于共病老人预防肌少症。由于数据限制，未来可通过纵向研究探究更多预测因素以指导干预设计；同时合适睡眠时长和具体身体活动强度与共病老人肌少症异质性轨迹关系也等待挖掘。
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  • 广东省基础与应用基础研究基金资助项目(2023A1515012522)
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参考文献 引证文献
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doi: 10.20043/j.cnki.MPM.202402002
  • 接收时间：2024-02-01
  • 首发时间：2026-03-17
  • 出版时间：2024-06-25
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    中山大学护理学院，广东 广州 510000

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